5-bromo-2-methoxy-6-(methylamino)nicotinic acid → 5-Bromo-N-[(6R)-1-ethylhexahydro-4-methyl-1H-1,4-diazepin-6-yl]-2-methoxy-6-(methylamino)-3-pyridinecarboxamide

HRID 1586379Notes

Reaction equation

HRID 1586379 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=O)[C:5]([O:10][CH3:11])=[N:6][C:7]=1[NH:8][CH3:9].[NH2:15][C@H:16]1[CH2:22][N:21]([CH2:23][CH3:24])[CH2:20][CH2:19][N:18]([CH3:25])[CH2:17]1>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([C:12]([NH:15][C@H:16]2[CH2:22][N:21]([CH2:23][CH3:24])[CH2:20][CH2:19][N:18]([CH3:25])[CH2:17]2)=[O:14])[C:5]([O:10][CH3:11])=[N:6][C:7]=1[NH:8][CH3:9]

Participants

4

Reactant 2

HCID 107538715-bromo-2-methoxy-6-(methylamino)nicotinic acidHCID 11116313(R)-6-amino-1-ethyl-4-methylhexahydro-1H-1,4-diazepine

Product 1

HCID 98439105-Bromo-N-[(6R)-1-ethylhexahydro-4-methyl-1H-1,4-diazepin-6-yl]-2-methoxy-6-(methylamino)-3-pyridinecarboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A liquid mixture of 18.0 g of 5-bromo-2-methoxy-6-methylamino-3-pyridinecarboxylic acid, 11.7 g of N,N'-carbonyldiimidazole and 50 ml of dimethylformamide was stirred for at room temperature 8 hours. To the reaction mixture then 13.0 g of (R)-6-amino-1-ethyl-4-methylhexahydro-1H-1,4-diazepine was added, followed by 15 hours' stirring at room temperature. The reaction mixture was concentrated under reduced pressure, and to which an aqueous 2N sodium hydroxide solution was added, followed by extraction with chloroform. The extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, eluted and purified with chloroform-methanol (15:1) and recrystallized from diethyl ether to provide 19.6 g of (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide 1/4 hydrate (m.p. 52-55° C.).

Workup

  1. waitfollowed by 15 hours
  2. stirring' stirring at room temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionto which an aqueous 2N sodium hydroxide solution was added
  5. extractionfollowed by extraction with chloroform
  6. washThe extract was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. washeluted
  10. custompurified with chloroform-methanol (15:1)
  11. customrecrystallized from diethyl ether

Sources & evidence

ORD record
ord-d347399d966e4cd598573477cae1d300
Source dataset
uspto-grants-1999_08
Patent number
US05945415

Reaction notes

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